The Multifaceted Role of Adenosine in Experimental and Clinical Traumatic Brain Injury

  • Patrick M. Kochanek
  • Edwin K. Jackson
Part of the Molecular and Cellular Biology of Critical Care Medicine book series (MCCM, volume 2)

Abstract

Unfortunately, no therapy effective in experimental traumatic brain injury (TBI) has been successfully taken from bench to bedside. Implicating the possible importance of being able to simultaneously target deleterious cascades after severe TBI, a host of recent clinical trials of therapeutic agents targeting specific individual mechanisms have all failed, most notably even therapies targeting putative key mechanisms of secondary damage, such as excitotoxicity (Doppenberg et al. 1997; Morris et al. 1999) and oxidative stress (Muizelaar et al. 1993; Young et al. 1996; Marshall et al. 1998). However, even the powerful multifaceted benefits of hypothermia were insufficient to confer a breakthrough beneficial effect on long-term outcome, as applied in the constraints of a recent multi-center clinical trial (Clifton et al. 2001). The obvious potential value of being able to target and ameliorate the activation of multiple deleterious cascades after TBI suggests the need to seek out—in addition to hypothermia—putative pharmacological agents that might simultaneously or sequentially confer multiple beneficial effects in the injured brain. One endogenous mediator that fits this category is adenosine—which has the potential to favorably influence excitotoxicity, energy failure, hypoperfusion, calcium accumulation, seizures, acute inflammation, oxidative stress, apoptosis, and angiogenesis.

Keywords

Ischemia Lactate Histamine NMDA Theophylline 

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Patrick M. Kochanek
    • 1
  • Edwin K. Jackson
    • 1
  1. 1.Safar Center for Resuscitation Research and the Center for Clinical PharmacologyUniversity of Pittsburgh School of MedicinePittsburghUSA

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